Streptococcus pyogenes which is also known as Group A Streptococcus (GAS) is a Gram positive bacterial pathogen that is responsible for numerous diseases including relatively benign pharyngitis and skin infections to serious invasive diseases including necrotizing fasciitis and the post-infectious sequelae rheumatic fever, rheumatic heart disease and glomerulonephritis. Presently, there is no strategy for primary prevention that is proven to work in less-developed countries, so a vaccine is clearly needed. Some vaccine strategies under development may not be effective in less developed countries. Our long-term goal is the development of broad-spectrum global vaccine that prevents GAS infection and its associated diseases, including rheumatic fever. Our GAS vaccine candidate is based on a peptide antigen from the conserved region of the M-protein. We have four potential vaccine constructs that use this antigen, each of which has shown good immunogenicity, safety and protection in pre-clinical studies. There are three overall objectives for the work in the current application: (1) Progression of the most advanced of our constructs to clinical trials. At the conclusion of this work, we expect to have completed: (a) An initial phase I trial in adult volunteers in Australia. (b) A larger multicentre phase I trial in adult volunteers in Australia and adult volunteers in a developing country. (c) A small phase I trial in child volunteers in a developing country. (2) Further development of the conserved region peptide as an intranasal vaccine. (3) Field studies in a developing country to establish correlates of protection that may be used in phase II and III clinical trials of the conserved region peptide, and to establish a field site for these later-phase trials.